Interferon γ-inducible protein 10 -: A predictive marker of successful treatment response in hepatitis C virus/HIV-coinfected patients

Background: Elevated pretreatment interferon (IFN) gamma-inducible protein 10 (IP-10/CXCL10) levels are a marker of treatment nonresponse in hepatitis C virus (HCV)-mono infected patients. We undertook this study to determine if IP-10 is a marker of treatment outcome in HCV/HIV-coinfected patients. Methods: Nineteen HCV/HIV-coinfected patients were treated with weight-based pegylated (PEG) IFN alpha-2b (1.5 mu g/kg) once weekly plus weight-based ribavirin (1000 or 1200 mg) daily for up to 48 weeks. Plasma IP-10, monokine induced by IFN gamma/CXCL9 (Mig), and IFN-inducible T-cell alpha-chemoattractant/CXCL11 (I-TAC) levels were measured by enzyme-linked immunosorbent assay on samples obtained frequently during the first 3 PEG-IFN doses and throughout treatment. Results: Median pretreatment plasma IP-10 (interquartile range [IQR]) levels were significantly lower in virological responders (n = 6) at 217 (IQR: IS 1-301) pg/mL compared with nonresponders (n = 13) at 900 (IQR: 628-2048) pg/mL (P = 0.002), whereas pretreatment Mig and I-TAC levels did not differ significantly. Plasma IP-10 levels of 400 pg/mL before treatment and on days 7 and 14 could be used to identify likely coinfected PEG-IFN/ribavirin nonresponders. PEG-IFN-induced elevations in IP-10 were greater in virological responders than in nonresponders (-10-fold vs. -4-fold) after the first PEG-IFN dose. Conclusions: IP- 10 may be a biomarker of HCV treatment outcome in difficult- to-treat HCV/HIV-coinfected patients.